Immunology of the eye
Uveitis is characterized by an inflammation of the uveal tract of the eye and is responsible for approximately 15% of blindness in the US. Uveitis is considered to be mediated primarily by CD4+ T cells, with little information on the role of CD8+ T cells. Here, we identified significant differences in CD8+ T cell memory subsets in non-infectious uveitis patients using an unbiased flow cytometry based approach. To validate these results, we studied a larger cohort of patients and analyzed their CD8+ T cell memory subsets. Consistent with our initial findings, CD8+ T Effector Memory (TEM) cells were increased in uveitis patients as compared to healthy controls, with a concomitant decrease in CD8+ naïve T (TN) cells. Majority of the study participants had uveitis without any systemic autoimmune disease however these differences were evident regardless of whether uveitis was associated with a systemic immune mediated disease. The TEM subset in patients also expressed increased levels of CD57 and KLRG1 with decreased expression of CD28, exhibiting a senescent-like phenotype. Additionally, these senescent-like CD8+ TEM cells corelated with disease activity. Functionally, these cells were metabolically active and produced more TNFα upon stimulation with CD3/2/28 beads compared to healthy controls. These results shed a new light on the involvement of CD8+ T cells in uveitis and suggests CD8+ TEM cells could serve as a potential biomarker for disease activity.